IL-10 and IL-12 (P70) Levels Predict the Risk of Covid-19 Progression in Hypertensive Patients: Insights From the BRACE-CORONA Trial.

Background: Cardiovascular comorbidities such as hypertension and inflammatory response dysregulation are associated with worse COVID-19 prognoses. Different cytokines have been proposed to play vital pathophysiological roles in COVID-19 progression, but appropriate prognostic biomarkers remain lacking. We hypothesized that the combination of immunological and clinical variables at admission could predict the clinical progression of COVID-19 in hypertensive patients. Methods: The levels of biomarkers, including C-reactive protein, lymphocytes, monocytes, and a panel of 29 cytokines, were measured in blood samples from 167 hypertensive patients included in the BRACE-CORONA trial. The primary outcome was the highest score during hospitalization on the modified WHO Ordinal Scale for Clinical Improvement. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and biomarkers associated significantly with the primary outcome. Results: During hospitalization, 13 (7.8%) patients showed progression to more severe forms of COVID-19, including three deaths. Obesity, diabetes, oxygen saturation, lung involvement on computed tomography examination, the C-reactive protein level, levels of 15 cytokines, and lymphopenia on admission were associated with progression to severe COVID-19. Elevated levels of interleukin-10 and interleukin-12 (p70) combined with two or three of the abovementioned clinical comorbidities were associated strongly with progression to severe COVID-19. The risk of progression to severe disease reached 97.5% in the presence of the five variables included in our model. Conclusions: This study demonstrated that interleukin-10 and interleukin-12 (p70) levels, in combination with clinical variables, at hospital admission are key biomarkers associated with an increased risk of disease progression in hypertensive patients with COVID-19.

Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. Design, Setting, and Participants: A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). Interventions: Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. Results: Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). Conclusions and Relevance: Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04364893.

Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society.

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.

Efficacy of Dexrazoxane in Preventing Anthracycline Cardiotoxicity in Breast Cancer.

OBJECTIVES: The authors performed a systematic review and meta-analysis of randomized and nonrandomized trials on the efficacy of dexrazoxane in patients with breast cancer who were treated with anthracyclines with or without trastuzumab. BACKGROUND: Breast cancer treatment with anthracyclines and trastuzumab is associated with an increased risk of cardiotoxicity. Among the various strategies to reduce the risk of cardiotoxicity, dexrazoxane is an option for primary prevention, but it is seldom used in clinical practice. METHODS: Online databases were searched from January 1990 up to March 1, 2019, for clinical trials on the use of dexrazoxane for the prevention of cardiotoxicity in patients with breast cancer receiving anthracyclines with or without trastuzumab. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model meta-analysis. RESULTS: Seven randomized trials and 2 retrospective trials with a total of 2,177 patients were included. Dexrazoxane reduced the risk of clinical heart failure (RR: 0.19; 95% CI: 0.09 to 0.40; p < 0.001) and cardiac events (RR: 0.36; 95% CI: 0.27 to 0.49; p < 0.001) irrespective of previous exposure to anthracyclines. The rate of a partial or complete oncological response, overall survival, and progression-free survival were not affected by dexrazoxane. CONCLUSIONS: Dexrazoxane reduced the risk of clinical heart failure and cardiac events in patients with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and did not significantly impact cancer outcomes. However, the quality of available evidence is low, and further randomized trials are warranted before the systematic implementation of this therapy in clinical practice.

Implante transcateter de prótese valvular aórtica: perfil clínico e evolução de uma série consecutiva de 75 casos do registro conjunto Universidade de Bolonha/Hospital Sírio-Libanês / Transcatheter implantation of aortic valve prosthesis: clinical profile and course of a consecutive series of 75 cases of the Bologna University/Hospital Sírio-Libanês joint registry

Introdução: O implante transcateter de prótese valvular aórtica (ITVA) tem sido utilizado em nosso meio e em diversos países do mundo como alternativa ao tratamento conservador em pacientes com estenose aórtica grave e elevado risco cirúrgico. Objetivou-se descrever o perfil clínico basal e a mortalidade a curto e médio prazos de uma série consecutiva de casos tratados com ITVA em dois centros localizados, respectivamente, na Itália e no Brasil. Métodos: A população de estudo foi composta pelos primeiros 75 pacientes consecutivos com estenose valvar aórtica grave tratados com a prótese Medtronic CoreValve TM Revalving System (MCV – Medtronic, Minneapolis, Estados Unidos). Tipicamente, a indicação para o ITVA foi motivada pelo alto risco cirúrgico. A média de idade era de 82 anos, 55% eram mulheres, um terço apresentava doença pulmonar grave e 95% apresentavam insuficiência cardíaca sintomática. Resultados: Após o ITVA, houve redução significativa do gradiente transvalvar aórtico máximo (basal: 95,8 + 32,3 mmHg; pós-procedimento: 18,5 + 6,1 mmHg) e médio (basal: 45,9 + 16,9 mmHg; pós-procedimento: 10,4 + 5,2 mmHg) (P < 0,01 para ambos). Insuficiência aórtica moderada ou acentuada foi evidenciada em 7% dos casos após ITVA. A taxa de sobrevida global aos 30 dias foi de 91,6% e aos 12 meses, de 79%. Conclusões: O ITVA surge como um método terapêutico de grande relevância para portadores de estenose aórtica de alto risco cirúrgico. As taxas de sobrevida precoce e a médio prazo indicam o benefício potencial do novo procedimento também para pacientes tratados no chamado mundo real.

Background: Transcatheter aortic valve implantation (TAVI) has been used in our country and in several differentcountries worldwide as an alternative to conservative treatment for patients with severe aortic stenosis and high surgicalrisk. This paper aimed at describing the baseline clinical profile and the short and medium-term mortality of a consecutive series of cases treated with TAVI in two centers in Italy and Brazil, respectively. Methods: The study population included the first 75 consecutive patients with severeaortic stenosis treated with the Medtronic CoreValveTM Revalving System (MCV – Medtronic, Minneapolis, USA). Typically, the indication for TAVI was motivated by high surgical risk. Mean age was 82 years, 55% were females, a third had severe lung disease, and 95% had symptomaticheart failure. Results: TAVI was associated with a significant reduction of peak (baseline: 95.8 + 32.3 mmHg; postprocedure: 18.5 + 6.1 mmHg) and mean (baseline: 45.9 + 16.9 mmHg; post-procedure: 10.4 + 5.2 mmHg) transaortic gradient (P < 0.01 for both). Moderate or severe aortic insufficiencywas observed in 7% of the cases. The overall survival rate at 30 days was 91.6% and at 12 months it was 79%.Conclusions: TAVI emerges as an important therapeutic option for high risk patients with aortic stenosis. The short and mediumterm survival rates suggest that the new procedure might beof benefit for patients treated in the real world context.

Implante transcateter de valva aórtica sem a necessidade de marca-passo definitivo em uma série de casos consecutivos: é possível predizer o risco de bloqueio atrioventricular? / Transcatheter aortic valve implantatation without permanent pacemacker in a series of consecutive cases: is it possible to predict the risk of atrioventricular block?

Introdução: Embora os stents farmacológicos tenham reduzido de forma inconteste o crescimento neointimal e sua consequência clínica direta, a reestenose, questionamentos acerca de sua segurança a longo prazo têm motivado o desenvolvimento de novas tecnologias. A aplicação sistêmica de fármacos antiproliferativos teria o potencial de solucionar o problema da reestenose e ao mesmo tempo amenizar a questão da segurança tardia inerente aos polímeros sintéticos. Recentemente, estudo investigando a administração intravenosa de uma solução de paclitaxel ligado à albumina (ABI-007) produziu efeito discreto na redução da formação de tecido neointimal. Este trabalho teve como objetivo avaliar, por meio da angiografia e do ultrassom intracoronário (USIC) seriados, a efetividade da aplicação intracoronária do ABI-007 na supressão da hiperplasia neointimal após implante de stents não-farmacológicos. Método: Entre novembro de 2006 e maio de 2007, pacientes portadores de lesões coronárias de novo, com extensão < 18 mm, em vasos nativos de 2,5 mm a 3,5 mm de diâmetro, foram submetidos a intervenção coronária percutânea com implante de stents não-farmacológicos, seguida de injeção intracoronária de 70 mg/m² de ABI-007. Avaliação com angiografia e USIC foi programada para todos os pacientes imediatamente após o procedimento e aos seis meses de seguimento. Desfecho primário era a perda luminal tardia (QCA) e o porcentual de obstrução volumétrica gerado pela hiperplasia neointimal (USIC) aos seis meses...

Background: Transcatheter aortic valve implantation (TAVI) is increasingly reported as a valid alternative therapeutic option for patients with aortic valve stenosis with highsurgical risk. Although effective and relatively safe, TAVI is currently associated to the need of permanent pacemaker in 20% to 30% of the cases, with a number of predictors of this complication already described in the literature. Method: We report a series of 8 consecutive patients with aortic stenosis treated with TAVI (Corevalve Revalving, Medtronic Inc., USA). Results: The study population had ahigh surgical risk (on average, STS Score = 22.9% and EuroSCORE = 27.2%). All cases presented at least onehigh-risk predictor for post-procedure high grade atrioventricular block. The interventional procedure was successfully accomplished in all but one patient who presented a cardiac tamponade and in-hospital death. The transaortic pressure gradient was reduced from 91.3 ± 26.9 mmHg to19.4 ± 6.3 mmHg. After hospital discharge, the follow-up time ranged from 4 weeks to 12 months. During follow-up, there were no deaths and none of the patients had a new 2nd or 3rd degree atrioventricular block and permanent pacemaker was not required in any of the cases. Conclusion: Although the lack of a permanent pacemaker in the study population may have occurred by chance, our initial experience suggests that the need of pacemaker following TAVI is not readily predictable with the currently described high-risk predictors.